ONP-302 Nanoparticles Inhibit Tumor Growth By Altering Tumor-Associated Macrophages And Cancer-Associated Fibroblasts

In this study, we evaluated the ability of negatively charged bio-degradable nanoparticles, ONP-302, to inhibit tumor growth. Therapeutic treatment with ONP-302 in vivo resulted in a marked delay in tumor growth in three different syngeneic tumor models in immunocompetent mice. ONP-302 efficacy persisted with depletion of CD8+ T cells in immunocompetent mice and also was effective in immune deficient mice. Examination of ONP-302 effects on components of the tumor microenvironment (TME) were explored. ONP-302 treatment caused a gene expression shift in TAMs toward the pro-inflammatory M1 type and substantially inhibited the expression of genes associated with the pro-tumorigenic function of CAFs. ONP-302 also induced apoptosis in CAFs in the TME. Together, these data support further development of ONP-302 as a novel first -in-class anti-cancer therapeutic that can be used as a single-agent as well as in combination therapies for the treatment of solid tumors due to its ability to modulate the TME.

Automated summary

In this study, the researchers evaluated the effectiveness of negatively charged bio-degradable nanoparticles called ONP-302 in inhibiting tumor growth. The results showed that treatment with ONP-302 significantly delayed tumor growth in immunocompetent mice in three different tumor models. ONP-302 also caused a shift in gene expression in tumor-associated macrophages (TAMs) towards the pro-inflammatory M1 type and inhibited the expression of genes associated with the pro-tumorigenic function of cancer-associated fibroblasts (CAFs). This study supports the further development of ONP-302 as a potential anti-cancer therapeutic agent.